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Abstract Title:

The citrus flavanone naringenin attenuates zymosan-induced mouse joint inflammation: induction of Nrf2 expression in recruited CD45hematopoietic cells.

Abstract Source:

Inflammopharmacology. 2019 Jan 5. Epub 2019 Jan 5. PMID: 30612217

Abstract Author(s):

Allan J C Bussmann, Sergio M Borghi, Tiago H Zaninelli, Telma S Dos Santos, Carla F S Guazelli, Victor Fattori, Talita P Domiciano, Felipe A Pinho-Ribeiro, Kenji W Ruiz-Miyazawa, Antonio M B Casella, Josiane A Vignoli, Doumit Camilios-Neto, Rubia Casagrande, Waldiceu A Verri

Article Affiliation:

Allan J C Bussmann

Abstract:

BACKGROUND: Naringenin is a biologically active analgesic, anti-inflammatory, and antioxidant flavonoid. Naringenin targets in inflammation-induced articular pain remain poorly explored.

METHODS: The present study investigated the cellular and molecular mechanisms involved in the analgesic/anti-inflammatory effects of naringenin in zymosan-induced arthritis. Mice were pre-treated orally with naringenin (16.7-150 mg/kg), followed by intra-articular injection of zymosan. Articular mechanical hyperalgesia and oedema, leucocyte recruitment to synovial cavity, histopathology, expression/production of pro- and anti-inflammatory mediators and NFκB activation, inflammasome component expression, and oxidative stress were evaluated.

RESULTS: Naringenin inhibited articular pain and oedema in a dose-dependent manner. The dose of 50 mg/kg inhibited leucocyte recruitment, histopathological alterations, NFκB activation, and NFκB-dependent pro-inflammatory cytokines (TNF-α, IL-1β, and IL-33), and preproET-1 mRNA expression, but increased anti-inflammatory IL-10. Naringenin also inhibited inflammasome upregulation (reduced Nlrp3, ASC, caspase-1, and pro-IL-1β mRNA expression) and oxidative stress (reduced gp91mRNA expression and superoxide anion production, increased GSH levels, induced Nrf2 protein in CD45hematopoietic recruited cells, and induced Nrf2 and HO-1 mRNA expression).

CONCLUSIONS: Naringenin presents analgesic and anti-inflammatory effects in zymosan-induced arthritis by targeting its main physiopathological mechanisms. These data highlight this flavonoid as an interesting therapeutic compound to treat joint inflammation, deserving additional pre-clinical and clinical studies.

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